OVERALL ? SUMMARY/ ABSTRACT Alzheimer?s disease and related dementias (ADRD) together constitute a paramount and growing public health issue with tremendous cost and unfathomable aggregate suffering. Unless the diseases can be effectively treated or prevented, increased prevalence with changing demographics will lead to costs the country will find difficult to bear. Reflecting this national imperative, the National Alzheimer?s Project Act (NAPA) created a roadmap and goal to impact this disease by 2025. The current proposal for renewed funding of the UCSD Shiley-Marcos Alzheimer?s Disease Research Center (ADRC) explicitly aligns with NAPA and leverages the center?s deep roots and engagement built over the past 35 years. The center?s rich academic and community environment make it well positioned to synergize with the ADC network toward achievement of NAPA goals and milestones, particularly along the theme of examining heterogeneity of ADRD through the study of models, markers, and mechanisms in a diverse cohort of volunteers. Specifically, the center proposes work that will bring world-class advanced translational neurosciences to the study of heterogeneity and diversity in ADRD using new models and new, tailored community engagement approaches. including innovative disease in a dish models fostered by its new iPSC Core, and increased engagement with the Latino Amerindian community through the establishment of a Latino Core. Efforts are tightly integrated with functions of other cores bolstered by tremendous resources and experience gained over the center?s longstanding existence, while incorporating the most innovative, disruptive and cutting-edge science available on the multi- faceted UCSD campus. The center will achieve the following overarching aims unifying its broad-based activity in research, education, engagement, and sharing and synergizing with the ADC network: The center will 1) apply well-developed and interactive cores to foster cross-disciplinary, integrative, and innovative clinical and translational science, 2) educate and train a diverse workforce, 3) Provide a hub for scientific and community exchange and support, optimizing core efforts and synergies to best serve the local and broader patient, caregiver, and research communities and 4) engage in collaborative research across centers, with special emphasis on applying center strengths to complement the ADC network and extend its impact.